Recombinant Human Pro-Neuregulin-1, Membrane-Bound Isoform (NRG1) Protein (His), Active

Name: Recombinant Human Pro-Neuregulin-1, Membrane-Bound Isoform (NRG1) Protein (His), Active
Brand: Beta LifeScience
SKU: BLC-05832P
Availability: InStock

Greater than 95% as determined by SDS-PAGE.

Activity Measured by its binding ability in a functional ELISA. Immobilized NRG1 at 2 μg/ml can bind human ERBB3, the EC 50 is 18.24-23.66 ng/ml. Biological Activity Assay

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Product Overview

Description	Recombinant Human Pro-Neuregulin-1, Membrane-Bound Isoform (NRG1) Protein (His), Active is produced by our Mammalian cell expression system. This is a protein fragment.
Purity	Greater than 95% as determined by SDS-PAGE.
Endotoxin	Less than 1.0 EU/ug as determined by LAL method.
Activity	Measured by its binding ability in a functional ELISA. Immobilized NRG1 at 2 μg/ml can bind human ERBB3, the EC 50 is 18.24-23.66 ng/ml.
Uniprotkb	Q02297
Target Symbol	NRG1
Synonyms	(Pro-NRG1)(GGF)(HGL)(HRGA)(NDF)(SMDF)
Species	Homo sapiens (Human)
Expression System	Mammalian cell
Tag	C-6His
Target Protein Sequence	SGKKPESAAGSQSPALPPRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDSASANITIVESNEIITGMPASTEGAYVSSESPIRISVSTEGANTSSSTSTSTTGTSHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKHLGIEFMEAEELYQKR
Expression Range	20-247aa
Protein Length	Partial of Isoform 6
Mol. Weight	27.1 kDa
Form	Lyophilized powder
Buffer	Lyophilized from a 0.2 μm filtered 20 mM Tris-HCl, 0.5 M NaCl, 6% Trehalose, pH 8.0
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4. Binds to ERBB3. Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1. Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.
Subcellular Location	[Pro-neuregulin-1, membrane-bound isoform]: Cell membrane; Single-pass type I membrane protein. Note=Does not seem to be active.; [Neuregulin-1]: Secreted.; [Isoform 8]: Nucleus. Note=May be nuclear.; [Isoform 9]: Secreted. Note=Has a signal peptide.; [Isoform 10]: Membrane; Single-pass type I membrane protein. Note=May possess an internal uncleaved signal sequence.
Protein Families	Neuregulin family
Database References	HGNC: 7997 OMIM: 142445 KEGG: hsa:3084 STRING: 9606.ENSP00000349275 UniGene: PMID: 28496106 In Autism Spectrum Disorder patients, the NRG1 levels were found to be statistically significantly high compared to the healthy control group. PMID: 30150060 COMT-GG and NRG1-AA genotypes aid the transcranial direct current stimulation-induced improvement in auditory verbal hallucinations in schizophrenia patients. PMID: 29559020 The neuregulin1 was observed to be cleaved, adding to the 3 known NS3/4A cleavage targets. It showed that NS3/4A triggers an increase in neuregulin1 mRNA levels in HCV infected cells. PMID: 29438748 These results support the association between genetic variation of RET and NRG1 and susceptibility to Hirschsprung disease in the Chinese population. PMID: 28256518 Results found that NRG1, a potential prognostic marker is highly expressed in papillary thyroid cancer (PTC). Also, further data demonstrate that NRG1 activates the antioxidant pathway by upregulating the expression of antioxidant enzymes through NRF2, thus modulating redox homeostasis in PTC. PMID: 29901070 Mesenchymal stem cell-drived paclitaxel resistance in ErbB2/ErbB3-coexpressing breast cancer cells could be attributed to upregulation of Survivin via paracrine effect of NRG-1/ErbB3/PI-3K/Akt signaling, as either specific knockdown expression of ErbB3, or blocking of downstream PI-3K/Akt signaling, or specific inhibition of Survivin can completely reverse this effect. PMID: 29715459 The data suggest a role for transcriptional regulation of NRG1 in the predisposition to papillary thyroid carcinoma. PMID: 29121253 NRG1rs3924999 and NRG1 rs6994992 are associated with change of temperament scores in a clinical sample of subjects with major depression (MDD), who received selective serotonin reuptake inhibitor treatment. PMID: 29310728 NRG1 is a potential prognostic and therapeutic biomarker in gastric cancer patients PMID: 28573357 Study found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex of patients with symptomatic epilepsy. Also, NRG1-ErbB4 signaling suppresses GluN2B phosphorylation by Src inhibition. GluN2B is closely related to synaptic activity and its regulation by the NRG1-ErbB4-Src signaling axis highlights the importance of NRG1-ErbB4 signaling in symptomatic epilepsy pathology. PMID: 28273943 Levels of NRG1 type III expression in peripheral blood mononuclear cells were positively correlated with impairments in social interaction in children with autism spectrum disorder. PMID: 28089559 NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-overexpressing breast cancer cells. HER3 monoclonal antibody combined with trastuzumab may serve as a treatment choice for patients with primary resistance to trastuzumab. PMID: 29048656 Results represent the first comprehensive investigation of neuregulin-1 (NRG1) isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia. PMID: 29225331 HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer PMID: 27941874 Date indicate the subcellular localization and dynamics post-translational processing, (ectodomain shedding) of neuregulin1 (NRG1). PMID: 27364328 NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls. PMID: 28430337 The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. PMID: 28600476 Using time-resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies is decreased. PMID: 28507002 Data suggest that SLC3A2-NRG1 should be considered a therapeutic target for patients with invasive mucinous adenocarcinoma of the lung (IMA). PMID: 27626312 we show that ErbB3 interacts with the ESCRT-0 subunit Hrs both in the presence and absence of heregulin. This indicates an ESCRT-mediated sorting of ErbB3 to late endosomes and lysosomes, and in line with this we show that impaired ESCRT function leads to an endosomal accumulation of ErbB3. PMID: 28867611 NRG1 genotype is associated with substance use. PMID: 27353026 Significant genetic risk for Hirschsprung disease (HSCR) was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3 in a Chinese population. No evidence was found of a genetic association between HSCR and either of the NRG1 SNPs rs7835688 and rs16879552, at either allele or genotype level. PMID: 27203398 High HRG1 expression is associated with breast cancer. PMID: 26885614 Results showed that heregulin-1ss mRNA was downregulated in 82 % of patients with hepatocellular carcinoma. PMID: 27514687 NRG1/ErbB2/Src/PTK2 signaling pathway may be a novel regulator of keloid fibroblast migration. PMID: 27882385 The plasma soluble NRG1 level was significantly higher in mild and moderate Alzheimer's disease patients compared to controls. PMID: 27133777 Data indicate a role for AXL receptor tyrosine kinase (AXL) in regulating the nuclear translocation of epidermal growth factor receptor (EGFR) and suggest that AXL-mediated SRC family kinases (SFKs) and neuregulin-1 (NRG1) expression promote this process. PMID: 28049763 NRG1FISH detection should be considered in patients with IMA pan-negative for known driver oncogenes. These results might suggest that NRG1 fusion is more frequent in IMA from Asian patient. PMID: 27770508 Results suggest genetic variation at the 5' and 3' ends of NRG1 are associated with schizophrenia. [Meta-Analysis] PMID: 28094814 Nrg1 acts as an axonal signal that drives virtually all stages of Schwann cell development and myelination.Nrg1 plays important role in the peripheral nerve injury and nerve repair.[review] PMID: 26970613 We also demonstrate that the effects of RET and NRG1 are universal across European and Asian ancestries. In contrast, we detected a European-specific association of a low-frequency variant, rs80227144, in SEMA3. Conditional analyses on the lead SNPs revealed a secondary association signal, corresponding to an Asian-specific, low-frequency missense variant encoding RET p.Asp489Asn PMID: 27702942 primary aromatase inhibitor treatment modulates expression of HER-family members as well as EGFR1 and NRG1 in HER-2/neu non-amplified breast cancers in vivo PMID: 27343990 GGF2 may improve contractile performance in the failing rat heart and that infrequent exposure to GGF2 may improve LV function PMID: 27993643 these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD. PMID: 27486021 Orbitofrontal sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment. PMID: 26909665 This study found a significant association between genetic variation at NRG1 and the modulation of small-worldness properties of the functional cortical network during the performance of an odd-ball task in healthy subjects. PMID: 26650688 Neuregulin-1 has now been accepted to have therapeutic potential in cardiovascular disease. The preclinical and clinical researches of NRG1 have demonstrated its advantage effects in cardiac function with multi-target cardiovascular biology and pathophysiology, but its influence on cardiac electrophysiology is rarely involved, which is a very important aspect and should not be ignored. [review] PMID: 26902151 Results suggest that silibinin is a potential anti-cancer drug to inhibit proliferative and invasive characteristics of the epithelial ovarian cancer (EOC) cells that exhibit an autocrine heregulin (HRG)/HER3 protein (HRG/HER3) pathway. PMID: 26482609 This population-based case-control study was carried out to determine whether polymorphisms in DISC1 and NRG1 genes could be associated with schizophrenia in the Chinese population. PMID: 27236031 SZuggest the use of polymeric PLGA and PEG-PLGA microparticles as delivery systems for NRG1 in the treatment of myocardial infarction. PMID: 26546270 NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. PMID: 26888291 overexpression of phospho-ALK and alternative receptor tyrosine kinases such as phospho-EGFR, phospho-HER3, and phospho-IGFR-1R was observed in both resistant cell lines. Additionally, NRG1, a ligand for HER3, is upregulated and responsible for resistance by activating the EGFR family pathways through the NRG1-HER3-EGFR axis. PMID: 26992917 Study found significant association between NRG1 (rs35753505) gene polymorphism and the risk of temporal lobe epilepsy in a Chinese Han population PMID: 26071373 Study shows that Neuregulin did not perform successfully as a biomarker for acute myocardial infarction or acute coronary syndrome in the emergency department. PMID: 27110055 This study demonstrate dysregulation of the NRG1-ErbB4/3 axis in both human and mouse ALS and to provide support for NRG1 supplementation as a possible therapeutic option for motor neuron disease PMID: 26891847 Data show that isoform beta2 of the heregulin (HRGbeta2) localizes at telomeres with the telomere-associated proteins TRF2 and RAP1. PMID: 26318724 Data indicate telomere-binding protein RAP1 as an interacting partner of isoform beta2 of the heregulin (HRGbeta2). PMID: 26327598 findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development. PMID: 26490994 Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. PMID: 26535009

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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